Biology subjects

Derbise, A.

Publications and source records attributed to Derbise, A..

5 recordsLinked to original sources

bioRxiv2026

Yersinia pestis lipoprotein SlyB promotes plague pathogenesis via envelope stress tolerance

Yersinia pestis, the etiological agent of plague, persists in an enzootic cycle involving mammals and fleas, requiring constant outer membrane (OM) adaptation to disparate host environments. One such pathway involves the glycine zipper 2TM domain-containing protein SlyB, a central component of the OM stress response and PhoPQ virulence pathway. While the OM is critical for virulence, the role of the OM lipoprotein SlyB in Y. pestis ecology and pathogenesis remains unknown. We show by phylogenetic analyses that slyB paralogs expanded in environmental bacteria, whereas the canonical slyB gene was under negative selective pressure during Y. pestis speciation from Yersinia pseudotuberculosis. Using rodent and flea infection models recapitulating Y. pestis natural history, we demonstrate that SlyB is specifically required to resist the mammalian immune system at 37{degrees}C, including neutrophil-mediated antimicrobial activity during lymph node colonization, but is dispensable in septicemic plague in rodents. Strikingly, SlyB is not required for flea colonization and resistance to the antimicrobial-peptide-based immunity of arthropods at lower temperatures. SlyB-dependent OM stress tolerance reveals a mechanism by which Y. pestis establishes bubonic plague, in line with its critical lipopolysaccharide structural switch. Our findings identify SlyB as an evolutionarily fine-tuned component of the Y. pestis envelope that mediates immune escape upon infection of mammalian hosts through maintenance of structural integrity.

microbiology↗

bioRxiv2024

A type IVB secretion system contributes to the pathogenicity of Yersinia pseudotuberculosis strains responsible for the Far East scarlet-like fever

Yersinia pseudotuberculosis is a food-borne pathogen responsible for a self-limiting gastrointestinal disease in humans known as mesenteric lymphadenitis. A phylogenetically distinct Y. pseudotuberculosis cluster from lineages 1 and 8 is associated to a specific syndrome called the Far East scarlet-like fever (FESLF), characterized by skin rash, hyperemic tongue and desquamation. Genome sequencing of FESLF strains previously revealed the presence in the plasmid pVM82 of dot/icm genes, homologous to those known to encode a T4BSS in the intracellular pathogens Legionella pneumophila and Coxiella burnetii. In the present article, we characterized the genomic features and functionality of the Y. pseudotuberculosis T4BSS (yT4BSS). We found higher dot/icm gene identity between Y. pseudotuberculosis and Pseudomonas putida genes than with those of L. pneumophila or C. burnetii. We validated the presence of all essential dot/icm genes required for the structure of a T4BSS. We then evaluated the conditions required for yT4BSS gene expression in vitro and identified an influence of temperature, with higher expression at 37{degrees}C, which mimicks the mammalian host temperature. The yT4BSS is also expressed in cellulo during the Y. pseudotuberculosis intracellular life cycle and in vivo during mouse infection. Although T4BSS functions are well characterized in the intracellular life cycle of L. pneumophila and C. burnetii, the yT4BSS appears to not be required for the intracellular survival nor for the establishment of a replication niche within cells of Y. pseudotuberculosis. Interestingly, the yT4BSS is implicated in Y. pseudotuberculosis FESLF strain pathogenicity when orally inoculated to mice but not during intravenous inoculation. Despite a role in virulence during oral infection, the yT4BSS does not influence organ colonization. However, the yT4BSS appears to be implicated in induction of important necrosis lesions in mesenteric lymph nodes and caeca of mice. Cytokine profil analyses revealed an induction of production of innate immunity related cytokines and chemokines depending on the yT4BSS in cellulo using a mouse bone marrow-derived macrophages infection model. Thus, the yT4BSS modulates cytokine responses of the host innate immune system during oral infection. In conclusion, the yT4BSS is a newly characterized virulence factor implicated in pathogenicity of Y. pseudotuberculosis strains from lineage 8 responsible for FESLF.

microbiology↗

bioRxiv2024

Contribution of the Type 3 Secretion System to immunogenicity of a live Yersinia pseudotuberculosis plague vaccine

The causative agent of plague, Yersinia pestis, remains a treat for public health worldwide. In the perspective to develop effective and safe vaccines, we present here a derived version of our Y. pseudotuberculosis VTnF1 live attenuated vaccine candidate that lacks the pYV virulence plasmid coding for the Type 3 Secretion system (T3SS) and no antibiotic resistance cassettes. This strain, called VpYV-, was safe for immunodeficient mice, and thus can be considered as deeply attenuated. It still has tropism for lymphatic tissues (Peyers patches, Mesenteric lymph nodes) but hardly reaches the spleen and liver. It elicits IgG to the F1 antigen as efficiently as VTnF1 but less directed to other Yersinia antigens. A single oral dose induced 100% protection against bubonic and pneumonic forms of plague, but this protection decreased faster with time than that of VTnF1. In the same line, VpYV-was 30% less protective against a F1-negative Y. pestis, revealing that the tools encoded by pYV are mandatory to obtain a large spectrum protection. Finally, VTnF1 like the Y. pestis vaccine EV76 can induce protection against co-infected Y. pestis relying on host iron nutritional immunity", indicating a potential use as therapeutics of recent infection. In contrast VpYV-failed to do so, revealing an importance of the T3SS in this mechanism. Overall, VpYV- and its parental strain VTnF1 offer a choice between more attenuation and safety or vaccine performances. They give an alternative and may represent useful tools to prevent and treat Y. pestis infection in healthy or immunosuppressed individuals.

microbiology↗

bioRxiv2019

Subcutaneous vaccination with a live attenuated Yersinia pseudotuberculosis plague vaccine

A single oral inoculation to mice of the live attenuated Yersinia pseudotuberculosis VTnF1 strain producing an F1 pseudocapsule protects against bubonic and pneumonic plague. However oral vaccination can fail in humans exposed to frequent intestinal infections. We evaluated in mice the efficacy of subcutaneous vaccine injection as an alternative way to induce protective immunity, while reducing the dose and avoiding strain release in nature. A single subcutaneous dose of up to 108 CFU induced dose-dependent antibody production. At the dose of 107 CFU, i.e. 10 times less than via the oral route, it caused a modest skin reaction and protected 100% against bubonic and 80% against pneumonic plague, caused by high doses of Yersinia pestis. Bacteria migrating to lymph nodes and spleen, but not feces, were rapidly eliminated. Thus, subcutaneous injection of VTnF1 would represent a good alternative when dissemination in nature and human intestinal responsiveness are limitations.

immunology↗

bioRxiv2019

Bread feeding is a robust and more physiological enteropathogen administration method compared to oral gavage

Oral administration is a preferred model for studying infection by bacterial enteropathogens such as Yersinia. In the mouse model, the most frequent method for oral infection consists of oral gavage with a feeding needle directly introduced in the animal stomach via the esophagus. In this study, we compared needle gavage to bread feeding as an alternative mode of bacterial administration. Using a bioluminescence-expressing strain of Yersinia pseudotuberculosis, we detected very early upon needle gavage a bioluminescent signal in the neck area together with a signal in the abdominal region, highlighting the presence of two independent sites of bacterial colonization and multiplication. Bacteria were often detected in the esophagus and trachea, as well as in the lymph nodes draining the salivary glands, suggesting that lesions made during needle introduction into the animal oral cavity lead to rapid bacterial draining to proximal lymph nodes. We then tested an alternative mode of bacterial administration using small pieces of white bread containing bacteria. Upon bread feeding infection, mice exhibited a stronger bioluminescent signal in the abdominal region as compared to needle gavage, and no signal was detected in the neck area. Moreover, Y. pseudotuberculosis incorporated in the bread is less susceptible to the acidic environment of the stomach and is therefore more efficient in causing intestinal infections. Based on our observations, bread feeding constitutes a natural and more efficient administration method which does not require specialized skills, is less traumatic for the animal, and results in diseases that more closely mimic food-borne intestinal infection.

microbiology↗